Biomaterial structures can be used in fields including medical treatment and diagnosis, gene analysis, and proteomics, being specially suitable for tools such as affinity purification tools and analysis tools of pharmacological actions. Some reports have been made as to structures used for such tools as affinity purification tools and analysis tools of pharmacological actions.
Examples of the carriers conventionally used for affinity chromatography are: inorganic materials such as porous silica gel particles; particles made of natural macromolecules such as polysaccharides including agarose, dextran, and cellulose; and particles made of synthetic polymer such as polystyrene and polyacrylamide.
However, the use of these conventional affinity chromatography carriers for affinity purification often causes difficulty in inhibiting non-specific adsorption into the carriers for affinity chromatography; an increase in purity through purification involves a decrease in the efficiency of recovery.
To address these problems, methods of affinity purification using latex microparticles have been reported recently, as described in Patent Document 1. Since the method employs Brownian motion of the latex particles, a target object for purification can specifically be adsorbed to the surface of the latex microparticles with efficiency. In addition, the method has the advantage of requiring a small amount of sample, because the latex to which the target object is adsorbed can be recovered through centrifugation.
On the other hand, technologies are suggested which carry out separation magnetically without centrifugation. To attain the object, the lattices containing magnetic materials are developed (Patent Document 2, Non-Patent Document 1).
Patent Document 3 discloses biochemical microparticles composed of agglomerate lumps in which albumin insolubilized with glutaraldehyde is combined with antibodies or antigens.
In addition, solid-state carriers with immobilized biomaterials are known, and their applications are examined to fields including medical treatment and diagnosis, genes analysis, proteomics, microelectronics, and membrane separation, especially to the fields of biochips and biosensor chips such as DNA chips and protein chips.
Some reports have also been made as to methods of producing such solid-state carriers with immobilized biomaterials as described above, namely, methods of immobilizing biomaterials onto solid-state carrier surfaces.
To immobilize a biomaterial to a solid-state carrier, an example of the methods includes coating the surface of the solid-state carrier with hydrophilic polymer compound to form a polymer film on the solid-state carrier surface, after which the polymer chains composing the polymer film are bound to a biomaterial such as a ligand. Compared to the case where the solid-state carrier surface is not coated with a hydrophilic polymer compound, the method can advantageously improve the introduction amount (immobilization amount) of the biomaterial per unit area, and is therefore applied to a variety of fields as mentioned above.
Patent Document 4 discloses a method of forming a coating film of a hydrophilic polymer provided with an electrically-charged functional group. In accordance with the aforementioned method, in which a biomaterial such as a ligand is immobilized in a polymer film on a solid-state carrier, it is difficult to immobilize the biomaterial with high density due to its penetration into the polymer film. By contrast, the method disclosed in Patent Document 4 has an advantage in that if the pH of the solution is adjusted such that the surface charge of the biomaterial the polymer film is opposite to the charge of the electrically-charged functional group, the biomaterial to the polymer film can be acceleratedly immobilized through electrostatic interaction, resulting in high-density immobilization.
Commercially available products made through the method described in Patent Document 4 include a glass plate covered with gold and surface treated with a CM-dextran film (Sensor Chip CM5 manufactured by BIACORE).
Another commercially available product is a slide glass, which serves as a solid-state carrier, covered with a polyacrylamide film (HydroGel Coated Slide manufactured by PerkinElmer, Inc.). Since the product is prepared with polyacrylamide gel swelling due to water content, it is suitable for the purpose of dropping a sample in the order of nanoliters, which is easy to dry. Also advantageously, the product is in no need of activation because the biomaterial is adsorbed to the polyacrylamide.
Patent Document 5 discloses a method that includes mixing a polyurethane polymer with a biomaterial in an organic solvent and adding a condensing agent to the mixture so that the polymer is polymerized and bound to the surface of a basal plate. Different from the conventional complicated methods, the method can yield a film containing the biomaterial on the solid-state carrier surface through simple operations; the biomaterial is easily immobilized onto the solid-state carrier.
Patent Document 6 discloses a method in which monomers having activated ester groups are polymerized on a solid-state carrier to extend the polymer chains, and the resultant brush-like polymer chains formed on the solid-state carrier is coupled with a biomaterial. The method allows the immobilization of a biomaterial such as a ligand, and is in no need of activating the polymer chains for introduction (immobilization) onto the solid-state carrier.
As explained above, the conventional techniques for forming a hydrophilic polymer film on a solid-state carrier have their respective advantages.
On the other hand, Non-Patent Document 2, for example, discloses a method of immobilizing a biomaterial onto a solid-state carrier (microchannel wafer) on which a porous structure is formed in advance for increasing the surface area and allowing a larger amount of the biomaterial to be bound to the surface. Compared to the case where the solid-state carrier has a flat surface, the method can advantageously improve the introduction amount (immobilization amount) of the biomaterial per unit area, and is therefore applied to a variety of fields as mentioned above.    [Patent Document 1] Japanese Unexamined Patent Laid-Open Application Publication No. HEI 10-195099    [Patent Document 2] Japanese Unexamined Patent Laid-Open Application Publication No. 2003-327784    [Patent Document 3] Japanese Patent No. 2836009    [Patent Document 4] Specification of U.S. Pat. No. 5,242,828    [Patent Document 5] Specification of U.S. Pat. No. 6,174,683    [Patent Document 6] Pamphlet of WO 02/056021    [Non-Patent Document 1] Masanori ABE, Hiroshi HANDA, BIO INDUSTRY, Vol. 21, No. 8, p. 7.    [Non-Patent Document 2] Brandy J. Cheek, et al., Anal. Chem., 2001, 73, 5777-5783